MOTS-c regulates the ROS/TXNIP/NLRP3 pathway to alleviate diabetic cardiomyopathy.

Chronic low-grade inflammation is a characteristic of diabetes, which often culminates in cardiovascular events including myocardial damage, thereby increasing the risk of debilitating cardiac complications. The mitochondria-derived peptide MOTS-c regulates glucose and lipid metabolism while improving insulin resistance, making it a potential candidate for the treatment of diabetes and cardiovascular diseases. We investigated the impact of MOTS-c on cardiac structure and inflammation in diabetic rats induced by a high-sugar-fat diet combined with low-dose streptozotocin (30 mg/kg, i.p.). Our results confirm that high glucose levels activate the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome and increase reactive oxygen species (ROS), ultimately leading to myocardial injury. Furthermore, treatment with MOTS-c (0.5 mg/kg/day, i.p.) for 8 weeks reduced the expression of ROS/TXNIP/NLRP3 pathway proteins to inhibit the diabetic myocardial inflammatory response. These findings suggested that MOTS-c alleviates myocardial damage by inhibiting the ROS/TXNIP/NLRP3 pathway.